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Is tendon pathology a continuum? A pathology

model to explain the clinical presentation of
load-induced tendinopathy
J L Cook and C R Purdam
Br. J. Sports Med. 2009;43;409-416; originally published online 23 Sep 2008;
doi:10.1136/bjsm.2008.051193

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Review

Is tendon pathology a continuum? A pathology model

to explain the clinical presentation of load-induced
tendinopathy
J L Cook,1 C R Purdam2
1

Centre for Physical Activity and

Nutrition Research, School of
Exercise and Nutrition Sciences,
Deakin University, Melbourne,
Australia; 2 Department of
Physical Therapies, Australian
Institute of Sport, Canberra,
Australia
Correspondence to:
Dr Jill Cook, 221 Burwood
Highway, Melbourne 3025,
Australia; jill.cook@deakin.edu.
au
Accepted 18 August 2008
Published Online First
23 September 2008

ABSTRACT
Overuse tendinopathy is problematic to manage clinically.
People of different ages with tendons under diverse loads
present with varying degrees of pain, irritability, and
capacity to function. Recovery is similarly variable; some
tendons recover with simple interventions, some remain
resistant to all treatments.
The pathology of tendinopathy has been described as
degenerative or failed healing. Neither of these descriptions fully explains the heterogeneity of presentation. This
review proposes, and provides evidence for, a continuum
of pathology. This model of pathology allows rational
placement of treatments along the continuum.
A new model of tendinopathy and thoughtful treatment
implementation may improve outcomes for those with
tendinopathy. This model is presented for evaluation by
clinicians and researchers.

Overuse tendon injury (tendinopathy) occurs in

loaded tendons of the upper and lower limb and
results in pain, decreased exercise tolerance of the
tendon and a reduction in function. Characteristic
changes occur in tendon structure, resulting in a
tendon that is less capable of sustaining repeated
tensile load.
Tendon injury can occur in the mid-tendon, as in
the Achilles tendon; however, most tendon pathology and pain arise at the tendon attachment to
bone, such as the patellar tendon, medial and
lateral elbow tendon and tendons of the groin.
While the mid-tendon and the insertion are
morphologically different in the normal state, the
onset of pathology induces cell matrix changes that
are indistinguishable; that is, the pathology
appears to be the same.1 Despite a similar
pathology, it has been shown in the Achilles that
exercise specific for insertional or mid-tendon
tendinopathy provides improved clinical outcomes,
probably a reflection of the loading profiles in
different parts of the tendon.2 3
Load has been shown to be both anabolic and
catabolic for tendons.4 Repetitive energy storage
and release and excessive compression appear to be
key factors in the onset of tendinopathy. The
amount of load (volume, intensity, frequency) that
induces pathology is not clear; however, sufficient
time between loadings to allow a tendon to
respond to load appears important. Therefore
volume (hours) and frequency (sessions per day
or week) of intense load may be critical in the
capacity of both normal and pathological tendons
to tolerate load.5 Although load is a major pathoaetiological component, it is almost certainly
Br J Sports Med 2009;43:409416. doi:10.1136/bjsm.2008.051193

modulated by an interaction between intrinsic

factors such as genes, age, circulating and local
cytokine production, sex, biomechanics and body
composition.
Although loading history and individual factors
may influence the onset and amount of tendon
pathology, these are not generally considered when
developing a treatment plan for painful tendons.
Treatment for a first-time presentation of tendinopathy in a young athlete is often the same as that
offered to a postmenopausal woman with chronic
tendinopathy. The model proposed in this paper
hypothesises that the pathology and the response
to treatment are different in these presentations,
and that interventions should be tailored to the
pathology. Applying a single intervention to all
presentations of tendinopathy is unlikely to be
efficacious in every case.
This paper will examine existing concepts of
tendinopathy and then present a model for the
pathological process in tendon that collates existing knowledge. The model will be based on
evidence from clinical and basic science studies in
humans to demonstrate its validity.

EXISTING TENDON PATHOLOGY CONCEPTS

At least three states of tendon pathology have been
described to date. Following the demise of a
primary inflammatory model, tendinopathy was
considered to be degenerative. Degenerative tendinopathy is described variably; pathological terms
such as hypoxic degeneration, hyaline degeneration
and mucoid degeneration are used, all of which
suggest non-reparative, end-stage pathology.6 The
key features of degenerative pathology centre on
irreversible, degenerative cell changes and disintegration of the matrix.
Other authors have suggested that injured
tendon is in a healing phase, with active cells and
increased protein production, but with disorganisation of the matrix and neovascularisation. This
has been called failed healing7 or angiofibroblastic
hyperplasia.8
Failed healing and degeneration have been
associated with chronic overload, but pathology
has also been described when a tendon is unloaded
(stress-shielded). Unloading a tendon induces cell
and matrix change similar to that seen in an
overloaded state9 and decreases the mechanical
integrity of the tendon.10 In animals, this state has
been shown to be mostly reversible11; however, few
human studies have been conducted and tendon
unloading will not be considered further in this
paper.
409

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Review
Despite these varied descriptions of tendon pathology, the
possibility that these may be linked in a continuum has received
limited consideration.12 If a model of pathology can be
developed that is continually evaluated and modified in the
light of research findings, a better understanding of tendon
pathology, treatment and prevention is possible.

A NEW MODEL OF TENDON PATHOLOGY

We propose that there is a continuum of tendon pathology that
has three stages: reactive tendinopathy, tendon dysrepair (failed
healing) and degenerative tendinopathy (fig 1). The model is
described for convenience in three distinct stages; however, as it
is a continuum, there is continuity between stages.
Adding or removing load is the primary stimulus that drives
the tendon forward or back along the continuum, especially in
the early stages. Within the constraints of recovery proposed in
the model, reducing load may allow the tendon to return to a
previous level of structure and capacity within the continuum.13

What are the pathological, imaging and clinical manifestations at

each stage?
1. Reactive tendinopathy
It is proposed that reactive tendinopathy, a non-inflammatory
proliferative response in the cell and matrix, occurs with acute
tensile or compressive overload. This results in a short-term
adaptive and relatively homogeneous thickening of a portion of
the tendon that will either reduce stress (force/unit area) by
increasing cross-sectional area or allow adaptation to compression. This differs from normal tendon adaptation to tensile load,
which generally occurs through tendon stiffening with little
change in thickness.14

Clinically, reactive tendinopathy results from acute overload,

usually a burst of unaccustomed physical activity. Reactive
tendinopathy can also be seen clearly after a direct blow such as
falling directly onto the patellar tendon.15 This non-tensile, and
only transiently compressive, load induces considerable reaction
within the tendon cell and matrix.
Evidence that reactive tendinopathy occurs in response to
overload is fairly strong from in-vitro work.16 There is a
homogeneous, non-inflammatory cell response to load that
leads to metaplastic change in the cells and cell proliferation.
Tendon cells become more chondroid in shape, with more
cytoplasmic organelles for increased protein production. The
primary proteins are large proteoglycans, and this results in
matrix change due to an increase in bound water associated
with these proteoglycans. Collagen integrity is mostly maintained, although there can be some longitudinal separation, and
there is no change in neurovascular structures.
These initial changes in ground substance in reactive
tendinopathy may occur because quick adaptation is necessary
until longer-term change in either structure or mechanical
properties (true adaptation) happens. The quick response is
possible as larger proteoglycans associated with tendinopathy
(aggrecan and versican) and some glycoproteins (hyaluronan)
can be upregulated in a timespan varying from minutes to a few
days, much more quickly than the small proteoglycans of
normal tendon (20 days).17
Thus, reactive response is a short-term adaptation to overload
that thickens the tendon, reduces stress and increases stiffness.
The tendon has the potential to revert to normal if the overload
is sufficiently reduced or if there is sufficient time between
loading sessions.

Imaging
The tendon is swollen in a fusiform manner; the diameter is
increased on both magnetic resonance imaging (MRI) and
ultrasound (US) scans. Ultrasound shows reflection from intact
collagen fascicles, with diffuse hypoechogenicity occurring
between intact collagen structures. Magnetic resonance imaging
will show minimal or no increased signal at this stage. The
change in imaging appearance is mainly derived from the
increase in bound water within the proteoglycans (fig 2).

Clinical
Reactive tendinopathy is seen clinically in an acutely overloaded
tendon and is more common in a younger person. For example,
a young jumping athlete who dramatically increases the
number of jumping/landing repetitions a week may develop
patellar tendon swelling and pain.
Tendons chronically exposed to low levels of load (e.g. in the
detrained athlete returning from illness or injury, or a sedentary
person) may also be vulnerable to this stage of tendinopathy
when exposed to moderate increase in load. In addition it may
occur as a result of direct trauma to tendon, to which the
Achilles, patellar and elbow tendons are particularly exposed.

2. Tendon dysrepair

Figure 1 Pathology continuum; this model embraces the transition

from normal through to degenerative tendinopathy and highlights the
potential for reversibility early in the continuum. Reversibility of
pathology is unlikely in the degenerative stage.
410

Tendon dysrepair describes the attempt at tendon healing,

similar to reactive tendinopathy but with greater matrix
breakdown. There is an overall increase in number of cells,
which are mainly chondrocytic, as well as some myofibroblasts,
resulting in a marked increase in protein production (proteoglycan and collagen). The increase in proteoglycans results in
separation of the collagen and disorganisation of the matrix.
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Review
Figure 2 (A) Ultrasound image of a
thickened patellar tendon with intact
collagen fascicles. The arrow indicates
the width of the tendon. (B)
Histopathological appearance of reactive
tendinopathy/early tendon dysrepair. Note
the increased cell numbers and
intermittent cell rounding with some
evidence of increased ground substance
(light blue shading) (histology picture by
courtesy of F Bonar).

The changes are somewhat more focal and matrix changes more
varied than in the reactive stage. There may be an increase in
vascularity and associated neuronal ingrowth.18

intratendinous signal. The changes are more focal rather than

spread throughout the tendon.

Clinical
Imaging
The imaging changes reflect increased matrix disorganisation,
and these tendons are swollen, with increasing evidence of
collagen disorganisation. On US there is some discontinuity of
collagen fascicle and small focal areas of hypoechogenicity. The
increase in vascularity may be evident on colour or power
Doppler, and techniques to enhance vascularity (heat, exercise,
hanging the limb) (personal communication, Cormick, 2008)
may show a greater number of vessels. On MRI the tendon is
swollen and there is increased signal within the tendon.

This stage is primarily seen in the older person, but is seen in a

younger person or elite athlete with a chronically overloaded
tendon. The classic presentation is a middle-aged, recreational
athlete with focal Achilles tendon swelling and pain. The
tendon can have one or more focal nodular areas with or
without general thickening. Individuals with degenerative
changes often have a history of repeated bouts of tendon pain,
often resolving but returning as the tendon load changes.
Degenerative tendinopathy, if extensive enough, or if the
tendon is placed under high load, can rupture,22 consistent with
97% of tendons that rupture having degenerative change.23

Clinical
This pathology has been reported in chronically overloaded
tendons in the young,19 but may appear across a spectrum of
ages and loading environments. This stage may be hard to
distinguish clinically; these tendons are thick with more
localised changes in one area of the tendon. Tendon dysrepair
is best detected when imaging detects some focal structural
changes with or without increased vascularity.
The frequency, volume or length of time over which load has
been applied (ie, months or years of overload) may be important
variables. An older person with stiffer tendons that have less
adaptive ability may develop this stage of tendinopathy with
relatively lower loads. Some reversibility of the pathology is still
possible with load management and exercise to stimulate
matrix structure.20

3. Degenerative tendinopathy
This stage is clearly described in the literature, with progression
of both matrix and cell changes.8 Areas of cell death due to
apoptosis, trauma or tenocyte exhaustion are apparent.21 As a
result, areas of acellularity have been described, and large areas
of the matrix are disordered and filled with vessels, matrix
breakdown products and little collagen. There is little capacity
for reversibility of pathological changes at this stage. There is
considerable heterogeneity of the matrix in these tendons, with
islands of degenerative pathology interspersed between other
stages of pathology and normal tendon.

Imaging
The compromised matrix and the vascular changes can be
extensive. These appear on ultrasound scans as hypoechoic
regions with few reflections from collagen fascicles. Numerous
and larger vessels are usually visible on Doppler US. Magnetic
resonance imaging demonstrates increased tendon size and
Br J Sports Med 2009;43:409416. doi:10.1136/bjsm.2008.051193

EVIDENCE TO SUPPORT THIS MODEL

As longitudinal monitoring of histopathological change in
humans is ethically difficult, the stages and progressions
suggested in this model have been derived from integrating
evidence from cross-sectional studies and supported by findings
in animal models. Limited weight has been placed on outcomes
in animal studies, as animal tendons do not directly translate to
human tendinopathy. Longitudinal imaging studies in humans
allow tracking of tendon change over time, and these
demonstrate that some transition up and down the proposed
pathology model occurs. Finally, limited evidence is available
from clinical studies.
The concepts embedded in this model are strikingly similar to
those reported for articular cartilage pathology.24 In osteoarthritis Pollard et al proposed a continuum from a reversible stage
through to advanced osteoarthritis (table 1). The initial
response centred on reversible proteoglycan upregulation, initial
swelling and cellular upregulation, through to the latter stages
of irreversible heterogeneous tissue change including cell and
cartilage degeneration and erosion and subchondral bone
remodelling.

Histopathological studies
Evaluation of human asymptomatic tendons demonstrated that
cell change was always present when matrix change became
apparent.25 Additionally, matrix change was primarily in ground
substance, followed by collagen, and then (theoretically but not
demonstrated) in vascularity. This provides evidence for the
progression from normal to reactive response and tendon
dysrepair; however, this study did not examine tendons that
would be classified as degenerative. Although not considered a
good model for human overuse tendinopathy, animal studies
support these findings. Scott et al16 reported similar progression
in pathology in overloaded rat supraspinatus tendons.
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Review
Table 1 Stages of osteoarthritis
Feature

Reversible injury

Osteoarthritis

Ageing

Cartilage mass

Hypertrophy

No Change

Cartilage
topographic
distribution
Cartilage water
Cartilage collagen

Focal

Hypertrophy,
erosion
Focal.
Heterogeneous

Oedema
Reversible
deformation

Oedema
Degradation

Reversible
depletion
Resorption

Irreversible
depletion
Accumulative,
collagen,
proteoglycan
Increased activity
and proliferation
Mid focal superficial
inflammation

Dehydration
Increased advanced
glycation end
products
Reduced synthesis

Cartilage
proteoglycan
Cartilage matrix
degeneration
products
Cell activity
Synovium

Bone

Reversibly
increased
Mid focal
superficial
inflammation
No Change

Subchondral
remodelling

General, all layers

Accumulative:
oxidation. Glycation,
amyloid
Reduced
Atrophy

Osteopenia

Reproduced with permission and copyright of the British Editorial Society of Bone
and Joint Surgery. Pollard et al, 2008. The assessment of early osteoarthritis. J Bone
Joint Surg Br;90-B:41121.

Degenerative tendinopathy has been extensively described, but

the transition from dysrepair has not been demonstrated.

Imaging studies
Acute tendon response
An acute bout of exercise increased the MRI volume and signal
in abnormal Achilles tendon.26 This suggests several critical
things: tendon response is rapid, and tendon response is to
increase volume (circumference) and water (either bound as
part of ground substance or in vessels). This is the earliest form
of the reactive response to load proposed in this model.

Normal to reactive, and back

Several studies demonstrate both short-term and long-term
changes in the imaging appearance of tendons. Nearly half of
normal patellar tendons (with pain) became abnormal (mainly
reactive tendinopathy) in the presence of ongoing load over a
season of volleyball (high tendon load). A single tendon became
hypoechoic, suggesting transition through a reactive tendinopathy to tendon dysrepair/degenerative tendinopathy.27
Longitudinal imaging studies have consistently demonstrated
that between 10% and 30% of tendons reported as abnormal at
baseline become normal at follow-up.2830 This supports the
viability of a transition from reactive change back to normal
tendon.

Reactive to dysrepair
In a group of young athletes at risk of tendon overload and
pathology there was a subgroup with microhypoechoic areas on
US.19 This may represent a transition from reactive to tendon
dysrepair, where small islands of the tendon develop collagen
disorganisation. There is little evidence of reversal of this
transition in the longitudinal studies to date.

Dysrepair to degenerative tendinopathy

This transition is not clearly demonstrated in the literature, as
they are both considered abnormal and are not often identified
as separate entities. Imaging evaluation of highly loaded patellar
412

tendons in jumping athletes demonstrate that they primarily

transition towards abnormality and pain that is more apparent
in adults31 than in adolescents.32

Clinical studies
The cumulative effect of load on a tendon has been clearly
demonstrated when the tendon health of athletes who placed
high loads on their Achilles tendons in early adulthood was later
evaluated. Previous elite athletes had a higher cumulative
incidence of tendinopathy and rupture than age-matched
controls.33 As rupture represents end-stage degenerative tendinopathy,23 the higher rupture rates support high chronic load as
an important factor in tendon pathology. This also supports the
non-reversible nature of degenerative pathology, as these older
ex-athletes had not spontaneously recovered tendon health.
The inability of a tendon to recover once it reaches the
degenerative stage is supported by studies that have examined
tendons many years after injury or rupture. Although the
tendons may improve their function, they do not appear to
return to normal size or morphology. Several studies have
shown that large hypoechoic areas do not change,3436 and
similarly tendons used for anterior cruciate ligament graft
replacements remain abnormal for years.37

PLACING CLINICAL TREATMENTS IN THE PATHOLOGY MODEL

Deciding where a tendon is in the pathological spectrum
For ease of use clinically, we have divided the pathology into
two clear groups: reactive/early tendon dysrepair and late
tendon dysrepair/degenerative. This will allow most clinical
tendon presentations to be clearly placed in one of the two
categories based on clinical assessment.
Clinical and imaging features allow a tendon to be placed in
one of these two categories. An older person with a thick
nodular tendon is likely to have a degenerative tendon;
conversely, a young athlete after acute overload with a fusiform
swelling of the tendon will probably have a reactive tendinopathy. There are, however, tendons in which it may be clinically
difficult to stage the pathology, and in these tendons imaging
may give vital clues. If the tendon is generally swollen and
mildly hypoechoic or has small focal hypoechoic areas (one or
several) with no or minimal vascular changes, this indicates
reactive/early tendon dysrepair (fig 2). Tendons with large
discrete areas of hypoechogenicity, multiple vessels and more
focal swelling will be in the late tendon dysrepair/degenerative
category (fig 3).
This division of a continuum into two categories allows us to
have a nominal threshold beyond which tendons will not fully
return to normal structure. Cell dysfunction or death that
compromises matrix protein production and/or the inability of
the matrix to regain structural integrity results in a tendon
incapable of full repair. It has been demonstrated that even after
improvement in Achilles tendon pain and tendon structure and
vascularity after an eccentric exercise programme, the tendon
remains thicker than normal for several years.20

PLACING PAIN IN THIS MODEL OF TENDINOPATHY

Pain can occur at any point in this pathological model,
supporting the well-known dissociation between pain and
pathology in tendinopathy. Even tendons that appear normal
on imaging can be painful.27 Conversely, two-thirds of tendons
degenerative enough to rupture have been reported to be painfree before rupture.23
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Figure 3 (A) Ultrasound of a normal
right and tendon dysrepair/degenerative
left patellar tendon. Note the vessel
evident on power Doppler in the left
tendon, the hypoechoic area and the
tendon swelling. (B) Histopathological
appearance of late tendon dysrepair/
degeneration. Note the markedly
increased cell numbers, the loss of
collagen evidenced by the loss of
longitudinal rows of cells, and the
increase in vessels (histology picture by
courtesy of F Bonar).
The source of pain has been associated with neurovascular
ingrowth,38 seen in this model at the late tendon dysrepair/
degenerative phase. However, the fact that tendons can be painful
or pain-free anywhere in this model suggests another or
supplementary cause of pain that has so far proved elusive. The
presence of biochemical substances stimulated by overload
(compression or tension) and/or acting on sensitised nerves in
matrix seems to be one possibility. Cell production of substances
such as catecholamines, acetylcholine and glutamate acting on
their receptors, which allow autocrine/paracrine signalling, has
been described,39 which may explain pain in the cellularly active
stages in this model: reactive and tendon dysrepair.
Pain is the single clinical feature that the clinician seeks to
change, and pain response to treatment is a key indicator of
treatment success. If pain levels and response to load are
considered with the stage of pathology, treatment progression
and outcomes may improve.
Tendinopathic pain is induced by load and has two key
features: (1) dose-dependent pain in relation to singular or
cumulative load, and (2) pain that is well localised to the tendon
or enthesis. Increasing load on the tendon will usually increase
pain. During assessment, the tendon should be provocatively
loaded to functional levels to fully evaluate the level of pain.
Pain should be assessed in the context of the stage and level of
pathology; an extensively degenerated tendon with mild pain
can have insufficient integrity to tolerate high loads and has a
risk of rupture. Conversely, a proliferative tendinopathy is more
reactive and therefore assessment needs to be more conservative
when loading during assessment.

TREATMENT OF TENDINOPATHY
Clinical treatments directed at effecting change in tendon
structure or pathology are considered optimal interventions, but,
as pain is often the clinical presentation, a case can be made for
concentrating on reduction of pain as a valid outcome. It is evident
that pain can occur anywhere in the pathological continuum;
interventions that reduce pain and are also appropriate for the
stage of pathology should, therefore, be our ideal. Conversely,
inappropriate treatments for the stage of pathology (such as
loading up of a tendon in the proliferative phase of tendinopathy) may increase pain, leading to a poor clinical outcome.40
Common interventions and their proposed place in this model are
summarised in table 2. In an effort to maintain clarity of approach,
polymodal interventions, often undertaken in the clinical management of tendinopathy, have not been considered.

Reactive tendinopathy/early tendon dysrepair

Physical treatments
At this stage load management (reduction) will generally allow
the tendon time to adapt, the cells to become less reactive and
Br J Sports Med 2009;43:409416. doi:10.1136/bjsm.2008.051193

the matrix to resume a more normal structure. Also, a tendon

with reduced load is likely to have less pain. Identifying and
changing the abusive load may be as simple as allowing a day or
two between high or very high tendon loads. Assessment and
modification of the intensity, duration, frequency and type of
load is the key clinical intervention. This may include
identifying the potential for biomechanical overload. Studies
show that tendon response in type 1 collagen precursors peaks
around 3 days after a single bout of intense exercise, suggesting
that time interval for adaptive response is an important factor.41
Tendon load without energy storage and release, such as cycling
or strength-based weight training, can be maintained, as this is
less likely to induce further tendon response. Conversely, highload elastic or eccentric loading, particularly with little recovery
time (eg, on successive days), will tend to aggravate tendons in
this stage.

Pharmacotherapies
Non-steroidal anti-inflammatory medications (NSAIDs) have
been reported to retard soft tissue healing in a range of tissues.
Although pain may be reduced, they have a negative effect on
tendon repair.42 In reactive tendinopathy, this may be a
preferred effect, as tenocyte upregulation and excess ground
substance expression are apparent in this phase of tendinopathy.25 Ibuprofen (as well as indomethacin and naproxen
sodium) has been shown to inhibit expression of key ground
substance proteins responsible for tendon swelling (aggrecan) in
in-vitro tendon preparations.43 Ibuprofen and celecoxib are also
reported to have a specific effect in downregulating the cellular
response.44 45 Ibuprofen may be favoured as it has not been
shown to have a detrimental effect on ultimate tendon repair.42
Corticosteroids, primarily used to decrease pain, also decrease
cell proliferation and protein production and therefore could be
used in the reactive painful tendon. Repeated peritendinous
corticosteroid has been shown to reduce tendon diameter at 7
and 21 days after injection in tendons.46 Although peritendinous
injection is clinically accepted, it is not known whether
peritendon injection induces cell and matrix change within
the tendon.

Late tendon dysrepair/degenerative tendinopathy

Physical treatments
Treatments that stimulate cell activity, increase protein
production (collagen or ground substance) and restructure the
matrix are appropriate for this stage of tendinopathy. Exercise
interventions are discussed separately below.
Frictions have been proposed as an effective treatment in
tendon injury, and the rationale for their use, based on improving
tendon structure, fits into this stage of tendon pathology. They
have been shown to increase protein production in animals,47 but
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Table 2 Clinical and pharmacological treatments placed in the model
Stage

Pharmacological management

Physical management

Reactive
tendinopathy/early
tendon dysrepair

Tenocyte inhibitors (ibuprofen,

celecoxib, corticosteroid), aggrecan
inhibitors (ibuprofen, naproxen
sodium, indomethacin)
Prolotherapy (including blood),
aprotinin, sclerosing therapy,
glyceryl trinitrate

Load management.
Reduction in frequency
intensity of tendon load

Late tendon
dysrepair/
degeneration

Exercise with eccentric

component, ESWT,
frictions, ultrasound

ESWT, extracorporeal shock wave therapy.

in humans few stringent investigations have been conducted,48

and the results are variable. Clinically, compared with exercise,
frictions were less effective in reducing pain.49
Extracorporeal shock wave therapy (ESWT) has been shown
to have pain-relieving effects in a number of tendons, although
ESWT is not consistently shown to be superior to placebo
treatment. Studies in animal tendons show variable morphological and mechanical benefits and detriments from this
modality, but it may be of benefit in this stage of pathology.50
Ultrasound has been shown to increase protein production at
a tissue level.51 Similarly to frictions, it is less effective than
exercise in treating patellar tendinopathy.49 52
Surgery for chronic painful (presumably degenerative) tendons has produced varied outcomes, with 5080% of athletes
able to return to sport at their previous level.5355 Although
surgical techniques vary considerably, their results are not
dissimilar.56 Outcome after surgery was no better than eccentric
exercise57or ESWT58 for patellar tendinopathy. Surgery in nonathletic people produced poorer results than in active people.59
Despite these outcomes, surgery is considered a reasonable
option in those who have failed conservative interventions.

Pharmacotherapies
Treatments that stimulate a healing response in the tendon are
appropriate for degenerative tendinopathy. The injection of
various substances around or into the tendon or the process of
injection itself has been proposed to achieve this.
Prolotherapy using glucose and blood injections stimulates a
tissue response. Blood injection stimulates cell proliferation and
production of vascular endothelial growth factor,60 and it has
been demonstrated to induce matrix changes. Clinically, blood
injections have led to reduced vascularity and decreased tendon
diameter on ultrasound.61
Injection itself, regardless of the substances injected, has been
shown to have a beneficial effect on tendon structure. Multiple
tendon biopsies improved structural outcome in degenerative
tendons at 1 year compared with an untreated group,62 and
injections of active (polidocinol) and placebo (anaesthetic and
adrenaline) substances produced similar outcome.63
Aprotinin, a collagenase inhibitor, may preserve collagen in a
remodelling matrix. A recent randomised placebo-controlled
trial did not show benefits of aprotinin over placebo,64 although
earlier studies have shown an effect on pain.65
Sclerosing therapy has repeatedly been shown to be effective
in treating pain and improving structure in tendinopathy.66
When compared with placebo, both pain and structural
outcomes were significantly better with the sclerosing treatment in both Achilles and patellar tendon.67 Interestingly, the
effect on vessels appears to be delayed, with vascularity
increasing in the short term after treatment, suggesting that
the positive effect on pain may be through chemical neurolysis
rather than vascular change.68
414

Glyceryl trinitrate has been shown to effectively reduce

tendon pain in addition to the benefits of eccentric exercise.6971
It is reported to deliver increased amounts of nitric oxide to the
injured tendon, leading to improvement in collagen synthesis,
although a recent study has not demonstrated increased tissue
levels of NO or benefit from the treatment.72 These studies have
not examined the long-term effect of this treatment on tendon
structure or tendon vascularity.

PLACING EXERCISE IN THIS MODEL

Exercise, particularly eccentric exercise, has been shown to
affect both tendon structure and pain. Eccentric exercise has
been shown to increase collagen production in abnormal
tendons but not in normal tendons.73 Eccentric exercise has
been shown to improve tendon structure in both the short
term74 and the longer term20 and decrease tendon vessels.75
Eccentric exercise is an effective pain-relieving treatment, with
pain changing in the first 46 weeks.76 A meta-analysis reported
that eccentric exercise is beneficial for pain, function and return
to activity.77
In this model, for athletes in an earlier stage of tendinopathy,
who are already loading the tendon in a significant manner,
adding exercise (painful or not) may not improve outcome.41 78
This model hypothesises that exercise is a potent stimulus to
the already upregulated tendon cells and overstimulates a
fundamentally intact, but reactive (or sensitised), matrix. In
degenerative tendinopathy, exercise appears to be a positive
stimulus for cell activity and matrix restructuring.
In degenerative tendons, exercise-based treatments allow
variable levels of pain. The Alfredson eccentric exercise
programme suggests that pain during exercise in this stage
may be tolerated by the tendon.79 This is supported by
Silbernagel et al, whose study in a similar population allowed
activity pain of less than 5/10 during activity.80 There was no
difference in outcome when compared with a group that just
exercised without continuing activity. These studies suggest
that exercise that induces pain in the degenerative stage will not
affect outcome. If pain in degenerative tendinopathy is
mediated by neurovascular structures more than cellular
products, as this model suggests, then neurovascular pain
appears to be less reactive and tendons would be less irritable
in this stage of tendinopathy.

DISCUSSION
We present a simple and succinct model of tendon pathology,
which is consistent with the clinical presentations of tendinopathy. The aim of this model is to logically order treatment
options for clinicians. Although we have used the term loadinduced tendinopathy, we have deliberately not detailed what
type of load is responsible. Debate on the relative contribution
of tensile, compressive and combined loads is for other fora.
Although these are presented as discrete stages of pathology,
it is highly probable that some tendons may have discrete
regions that are in different stages at the one time. Examination
of tissue, particularly in the latter stages of pathology, often
reveals heterogeneous pathology in a single tendon.81 It is
possible that a tendon with degenerative change that is acutely
overloaded may develop reactive change in previously normal
parts of the tendon. Evaluating these more complex presentations has deliberately not been discussed in this paper to
maintain simplicity. Improving capacity to clinically evaluate
and treat these more difficult tendons is primarily dependent on
accepting the basic model presented.
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Review
Research into tendinopathy may also be improved by
considering this model. It is possible that the variable response
to tendon treatment in research studies may be explained to
some extent through the existence of subpopulations of
different pathologies in the investigated cohort. In fact, the
most consistent outcomes in research appear to occur when the
participants are clearly in one group, such as in Alfredsons
eccentric exercise research on older, presurgical patients.
Very little research has been conducted in early-stage
tendinopathy, possibly because of the inherent capacity of
these tendons to spontaneously recover, the variability of pain
presentation and the difficulties in assembling a sizeable cohort.
The individual factors considered earlier (genes, age, circulating and local cytokine production, sex, biomechanics and body
composition) may alter the progression forward or back in the
continuum82 and most are also likely to have an important role
in the response to treatment in tendinopathy. For example,
some athletes appear completely resistant to tendinopathy
despite high loads, and have never been shown to progress into
proliferative tendinopathy. Conversely, other athletes sustain
tendon ruptures relatively early in their careers, presumably
after some degenerative change in the tendon. Identifying
athletes at risk of tendon pathology, as well as using this model
in treatment, may improve outcomes. Early load management
in at-risk athletes may keep them in the early stages of tendon
pathology and limit progression.
Time to recovery should be inherent in a clinical model such
as this; however, the capacity for tendons to transition up and
down between stages makes time estimates for recovery
difficult. Overall, tendons respond very slowly, both in
improving load capacity and in resolving pain.

CONCLUSIONS
This model explains most clinical presentations and most
findings in the tendon literature. It can even encompass primary
collagen tearing83 and some form of inflammation underpinning
the cell and matrix response. Emerging mechanisms for injury,
complex interactions between the cell and matrix and systemic
and local factors (growth factors, cytokines and treatments) will
need to be built into this model. The integrity of the model will
only be as good as its capacity to withstand additional research.
This model now requires scientific and clinical evaluation.
Funding: Jill Cook was funded by a Club Warehouse Visiting Fellowship to the
Australian Institute of Sport Physical Therapies department. Club Warehouse had no
direct or indirect involvement in the production of this manuscript.

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Competing interests: None declared.

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